title: GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients.
abstract: BACKGROUND
  Recently, the analysis of gastric and colorectal tumor specimens determined that 78-kiloDalton glucose-regulated protein (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism protecting cells against apoptosis and can confer drug resistance. We tested whether functional polymorphisms within the GRP78 gene are related to clinical outcome in gastric and colorectal cancer (CRC) patients.
  
  
  METHODS
  Blood samples of 234 stage II/III CRC patients at the University of Southern California (USC) and formalin-fixed paraffin-embedded tissues of 137 patients with localized gastric adenocarcinoma (GA) at USC and Memorial Sloan-Kettering Cancer Centers were obtained. GRP78 polymorphisms analyzed on germline DNA were correlated with clinical outcome using univariate and multivariate analyses.
  
  
  RESULTS
  GA patients with the combined GRP78 rs391957 C/T and T/T genotype were at higher risk for tumor recurrence and death [hazard ratio (HR) 2.61; P < 0.001 and HR 3.17; P < 0.001, respectively], than those with C/C. These findings were subsequently tested in a CRC cohort where patients with the homozygous T/T genotype were at highest risk for tumor recurrence (HR 2.61; P = 0.015). The results remained significant after adjusting for clinicopathologic determinants.
  
  
  CONCLUSIONS
  These data provide the first evidence that the GRP78 rs391957 polymorphism can predict clinical outcome in localized GA and locally advanced CRC patients.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Winder
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: P
authors.initials: P
authors.lastname: Bohanes
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, Cornell University, New York.
authors.forename: D G
authors.initials: DG
authors.lastname: Power
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Gerger
authors.affiliation: Department of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles.
authors.forename: P M
authors.initials: PM
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, Cornell University, New York.
authors.forename: L H
authors.initials: LH
authors.lastname: Tang
authors.affiliation: Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, Cornell University, New York.
authors.forename: M
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology; Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles. Electronic address: lenz@usc.edu.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins